DEPOSITING FLUID SPECIMENS ON SUBSTRATES, RESULTING ORDERED ARRAYS, TECHNIQUES FOR ANALYSIS OF DEPOSITED ARRAYS
First Claim
1. An apparatus for deposit of fluid samples in an array of mutually isolated dots, comprising a deposit device, a fluid source for repeatedly providing a discrete drop of fluid on the deposit device, mechanism for moving the device relatively over an array of spaced apart deposit locations of a receiving substrate, mechanism for repeatedly moving the device, relatively, toward and away from the receiving substrate to deposit respective drops of fluid at respective deposit locations on the substrate by direct contact of drops of fluid on the deposit device with the substrate without direct contact of the deposit device with the substrate.
1 Assignment
0 Petitions
Accused Products
Abstract
Fluid is deposited in spots using supported, compliant pin arragements, supplied by a local reservoir. Pin arragements in the form of reciprocating and rotating devices are shown. Supply of the pins by mobile local subreservoirs limit the range of travel between drop-pickup and drop deposit. Local reservoirs in the form of circular rings and large pins are disclosed. Compliance is achieved by using spring and flexure arrangements. Some embodiments employ planer flexures to mount the pin and constrict its movement. Such deposit techniques are shown used in many analytical, reactive, and productive conditions. Combination of the use of the versatile, high density array or with a flying mini objective, wide field scanning microscope is disclosed. Combination with other sub systems adds to the versatility of the system.
81 Citations
98 Claims
- 1. An apparatus for deposit of fluid samples in an array of mutually isolated dots, comprising a deposit device, a fluid source for repeatedly providing a discrete drop of fluid on the deposit device, mechanism for moving the device relatively over an array of spaced apart deposit locations of a receiving substrate, mechanism for repeatedly moving the device, relatively, toward and away from the receiving substrate to deposit respective drops of fluid at respective deposit locations on the substrate by direct contact of drops of fluid on the deposit device with the substrate without direct contact of the deposit device with the substrate.
-
4. The apparatus of claim 1 wherein the fluid source includes a fluid storage device relative to which the deposit device repeatedly moves to resupply the device during the deposit of successive drops.
-
12. The apparatus of claim 5 constructed to produce relative resupply movement between the deposit device and the local storage device for the deposit of each discrete fluid drop.
- 31. An apparatus for deposit of fluid samples in a dense array of mutually isolated dots, comprising a deposit device, a fluid source for repeatedly providing fluid to the deposit device, mechanism for moving the device relatively over an array of spaced apart deposit locations of a receiving substrate, mechanism for repeatedly moving the deposit device, relatively, toward and away from the receiving substrate to deposit respective drops of fluid at respective deposit locations on the substrate, and a control system adapted to control relative movement of the deposit device to a deposit relationship with the substrate, wherein the deposit device is mounted on a flexure system which constrains the device to precise motion, and a driver is engaged to drive the deposit device to enable reciprocal motion, constrained by the flexure system, between retracted and extended positions depending upon the position of the driver.
-
36-1. An apparatus for deposit of fluid samples in a dense array of mutually isolated dots, comprising at least two deposit pins, at least one fluid source for repeatedly providing a drop of fluid on the end of each deposit pin, mechanism for moving the pins together transversely over an array of spaced apart deposit locations of a receiving substrate, mechanism for repeatedly moving each pin independently, relatively, toward and away from the receiving substrate to deposit respective drops at respective deposit locations on the substrate.
-
36-3. The apparatus of claim 22 in which at least four such pins and drivers are mounted on a deposit head.
- 37. The apparatus of claim 35 in which a relatively stiff flexure supports the deposit device via an intermediate relatively compliant flexure, the driver for the device engaged, effectively, with the relatively stiff flexure, and the deposit device being free to deflect relative to the stiff flexure by action of the compliant flexure, upon encountering resistance when moving toward the substrate.
-
37-2. The apparatus of claim 36 constructed to mount a number of microscope slides to serve as said substrate in deposit-receiving relationship, and a control system constructed and arranged to move the deposit pins in the manner to form deposits on more than one slide.
-
37-4. A deposit mechanism for deposit of biological fluid dots in an array, comprising a pin supported by a flexure, a source of biological fluid for deposit, and a driver engaged to drive the pin to enable reciprocal motion constrained, between retracted and extended positions depending upon the position of the driver.
-
38-5. The apparatus of claim 37 including a discrete local fluid supply for the pin.
-
40-7. The apparatus of claim 46 in which the local supply device is driven to enter a supply well and having a surface adapted to retain a supply of fluid by surface tension or capillar effects.
-
41-8. The apparatus of claim 40 in which a retaining surface of the local supply has surface roughness of at least 1000 microinch.
-
42-9. The apparatus of claim 41 in which a member has an inner annular surface having the surface roughness.
-
43-6. The apparatus in which two or more deposit pins according to claim 39 are grouped together for movement by a single drive as a corresponding member of members defining annular fluid retention surfaces according to claim 39 are associated respectively with respective pins, the members driven by a single drive member.
-
43-10. The apparatus of claim 44 in which the member has an outer surface that is by ______.
-
44-11. The apparatus of claim 41 sized and constructed to enter a well of a PCR plate and extract fluid by surface position or capillary efforts for supply to the deposit device.
- 45. The apparatus of claim 44 wherein the source includes a fluid storage device relative to which the deposit device repeatedly moves to resupply the device during the deposit of the isolated drops of fluid.
-
45-12. Apparatus for automated preparation of a microscope slide, comprising a microscope slide holder, a carrier operative over a slide on the holder, and a deposition head mounted on the carrier, the deposition head including a deposit pin constructed to carry a drop of fluid from a fluid supply, and mechanism constructed, in a deposit sequence, to move the deposit pin relative to the supply to pick up a drop of fluid, and move the deposit pin toward the microscope slide to completely deposit the drop of fluid on the slide, there being a control system arranged to repeat the deposit sequence to produce a high density of drops of deposited fluid upon the slide.
-
46-13. The device of claim 45 in which the deposit pin has a deposit end comprising an abrupt profile that defines the perimeter of the drop of fluid to be picked up.
-
47-14. The device of claim 46 in which the pin comprises a generally cylindrical shaft and an end rim.
-
48-15. The deposition head of claim 47 in which the end rim is defined by a generally planar butt end of the pin.
-
49-16. The device of claim 45 wherein the supply comprises a sub-reservoir mounted on the head, closely adjacent to the deposit pin.
- 56. Apparatus for deposit of fluid samples in a dense array of mutually isolated dots on a receiving surface comprising a deposit pin, a fluid source for repeatedly providing a drop of fluid on the end of the deposit pin, mechanism for moving the pin relatively over an array of spaced apart deposit locations of a receiving substrate, mechanism for repeatedly moving the pin, relatively, toward and away from a targeted point on the receiving substrate to deposit respective drops of fluid at respective deposit locations on the receiving surface, and means for stopping movement of the depositing pin toward the targeted point on the receiving surface while fluid remains between the end of the pin and the receiving surface.
- 65. An apparatus comprising a deposit pin constructed and arranged to deposit a first dot upon a substrate and thereafter, in registration, to deposit a second dot upon the first dot.
- 68. A fluid deposit arranger for transferring a drop of fluid to a substrate by engaging the drop with the substrate, the device mounted on a compliant spring for compliant engagement with the substrate and incorporating a motion damping member.
-
82. A deposit head including at least two flexure mounted pins, and a single actuator arranged to move the pins simultaneously from supply to deposit positions, the head mounted for lateral movement in both X and Y axes.
-
83. The deposit head of 82 in which the pins are spaced apart 9 mm.
- 84. A deposit head including at least two flexure mounted pins, each associated with its own actuator to be moved independently from supply to deposit position, the head mounted for lateral movement in both X and Y axes.
- 86. An aliquot carrier defining a fluid-retaining aperture through which a deposit device can transit to pick up a drop of fluid to be deposited, internal surfaces defining said aperture having a surface roughness that increases its wettability.
-
87-17. The carrier of claim 86 in which the surface roughness is at least 100 microinch.
- 88. A process of printing comprising, under computer control, moving at least one flexure mounted pin to selected X,Y positions, and depositing with said pin, a desired material.
- 92. A method of causing a biological compound to interact with another substance at a predetermined position on a substrate the step comprising depositing at least one of the compound or reagent in a precisely determined localized spot relative to the substrate by mechanically lowering a compliant pin, to which a drop of the compound or reagent is adhered by surface tension, toward the substrate until the drop contacts the substrate or a pre-applied compound on the substrate with the pin executing a controlled force of less than a gram thereon, and thereafter mechanically lifting the pin away from the substrate under conditions in which the fluid drop transfers to the substrate or the pre-applied compound on the substrate.
-
98. The method of depositing a biological fluid with a pin comprising supporting fluid within a ring by surface tension, and the pin is lowered through the ring in the manner that a relatively small drop of the reagent from the supply is adhered to the end of the pin by surface tension.
Specification